Abuse of cocaine is a widespread and severely deleterious public health problem. Although it is well established that there is substantial variability in an individual's response to cocaine exposure, we do not yet understand the mechanisms that mediate individual differences in the etiology of cocaine abuse and addiction. In particular, we do not understand why some individuals are resistant to the effects of cocaine and will consume cocaine at low rates whereas other individuals are relatively vulnerable to the effects of cocaine and will consume cocaine at high rates. In the present proposal, we will evaluate several novel biomarkers that may predict the vulnerability of an individual to abuse cocaine or to relapse following abstinence. We will evaluate these processes using drug self-administration (SA) and reinstatement of previously drug-maintained behavior in nonhuman primates, as these are well established animal models of cocaine abuse and relapse. Moreover, we propose to determine, in a highly systematic manner, whether the availability of specific brain proteins, the acute brain activational effects of cocaine, or the integrity of functional bran networks predicts cocaine abuse and relapse. We believe that these studies will have important public health implications because these techniques can be translated into use in human subjects, and they will allow physicians to individually tailor treatment plans based on the current status of the cocaine-dependent patient. PUBLIC HEALTH RELEVANCE: Abuse of cocaine is a widespread and severely deleterious public health problem, yet we do not understand the processes that govern an individual's propensity to abuse cocaine or to relapse once abstinence has been achieved. A better understanding of these processes would further the development of effective treatments for this disorder. In the proposed studies, we will use multimodal neuroimaging and a nonhuman primate model of cocaine abuse and relapse to determine novel vulnerability factors that predispose individuals to cocaine abuse and relapse.